The roles of assembly factors in mammalian mitoribosome biogenesis

Hilander, Taru; Jackson, Christopher B.; Robciuc, Marius R.; Bashir, Tanzeela; Zhao, Hongxia

doi:10.1016/j.mito.2021.07.008

Cited by 21 publications

(17 citation statements)

References 117 publications

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“…As aforementioned, LP-BN-PAGE-based CP helped identify a RNP complex containing the mt-SSU associated with several translation and transcription factors at ∼5.7 MDa ( Rugen et al, 2019 ). LP-gels could thus be very useful for further dissection of larger RNPs or those that are associated with many other factors as it has been commonly reported for translation and RNA-processing machineries ( Acestor et al, 2009 ; Hocine et al, 2010 ; Blombach et al, 2011 ; Doetsch et al, 2011 ; Sprink et al, 2016 ; Duss et al, 2019 ; Gopalakrishna et al, 2019 ; Hilander et al, 2021 ).…”

Section: Complexome Profiling: Perspectivesmentioning

confidence: 99%

Complexome Profiling—Exploring Mitochondrial Protein Complexes in Health and Disease

Cabrera‐Orefice

Potter²,

Evers

et al. 2022

Front. Cell Dev. Biol.

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Complexome profiling (CP) is a state-of-the-art approach that combines separation of native proteins by electrophoresis, size exclusion chromatography or density gradient centrifugation with tandem mass spectrometry identification and quantification. Resulting data are computationally clustered to visualize the inventory, abundance and arrangement of multiprotein complexes in a biological sample. Since its formal introduction a decade ago, this method has been mostly applied to explore not only the composition and abundance of mitochondrial oxidative phosphorylation (OXPHOS) complexes in several species but also to identify novel protein interactors involved in their assembly, maintenance and functions. Besides, complexome profiling has been utilized to study the dynamics of OXPHOS complexes, as well as the impact of an increasing number of mutations leading to mitochondrial disorders or rearrangements of the whole mitochondrial complexome. Here, we summarize the major findings obtained by this approach; emphasize its advantages and current limitations; discuss multiple examples on how this tool could be applied to further investigate pathophysiological mechanisms and comment on the latest advances and opportunity areas to keep developing this methodology.

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Section: Complexome Profiling: Perspectivesmentioning

confidence: 99%

Complexome Profiling—Exploring Mitochondrial Protein Complexes in Health and Disease

Cabrera‐Orefice

Potter²,

Evers

et al. 2022

Front. Cell Dev. Biol.

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“…Representation of mtSSU assembly pathway with snMRPs highlighted (adapted from (Bogenhagen et al, 2018; Ferrari et al, 2020; Hilander et al, 2021)).…”

Section: Supplementary Figures and Tablesmentioning

confidence: 99%

Supernumerary proteins of the human mitochondrial ribosomal small subunit are integral for assembly and translation

Hilander¹,

Monteuuis²,

Awadhpersad³

et al. 2022

Preprint

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Mitochondrial ribosomes (mitoribosomes) have undergone substantial structural remodelling throughout evolution. Compared to their prokaryotic counterparts, mitoribosomes show a substantial loss of ribosomal RNA, whilst acquiring unique protein subunits located on the periphery of the ribosomal subunit structures. We set out to investigate the functional properties of all 14 unique (mitochondrial-specific or supernumerary) human mitoribosomal proteins in the small subunit. Using genome editing with CRISPR-Cas9, we made knockouts for each subunit in HEK293 cells to study the effect on mitoribosome assembly and function in protein synthesis. Unexpectedly, we show that each supernumerary knockout leads to a unique mitoribosome assembly defect with variable impact on mitochondrial protein synthesis. Our data demonstrates that all supernumerary subunits are essential structural components except mS37. Surprisingly, we found the stability of mS37 was reduced in all our supernumerary knockouts of the small and large ribosomal subunits as well as patient-derived lines with mitoribosome assembly defects. We identified that a redox regulated CX9C motif in mS37 was essential for protein stability, suggesting a potential mechanism to regulate mitochondrial protein synthesis. Together, our findings support a modular assembly of the human mitochondrial small ribosomal subunit mediated by essential supernumerary subunits and identify a redox regulatory role involving mS37 in mitochondrial protein synthesis in health and disease.

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“…Eukaryotic ribosome formation involves synthesizing and assembling four rRNA molecules with 79 to 80 unique ribosomal proteins (r-proteins). More than 250 proteins and noncoding (ncRNA) molecules are required for this complex process ( 1 – 4 ). The number of ribosomes per cell (~10 5 in yeast, ~10 7 in humans) and their structural complexity make ribosome formation very resource-intensive.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Ribosome Assembly and Ribosome Translation Has Distinctly Different Effects on Abundance and Paralogue Composition of Ribosomal Protein mRNAs in Saccharomyces cerevisiae

et al. 2023

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The roles of assembly factors in mammalian mitoribosome biogenesis

Cited by 21 publications

References 117 publications

Complexome Profiling—Exploring Mitochondrial Protein Complexes in Health and Disease

Complexome Profiling—Exploring Mitochondrial Protein Complexes in Health and Disease

Supernumerary proteins of the human mitochondrial ribosomal small subunit are integral for assembly and translation

Inhibition of Ribosome Assembly and Ribosome Translation Has Distinctly Different Effects on Abundance and Paralogue Composition of Ribosomal Protein mRNAs in Saccharomyces cerevisiae

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